Abstract: The commensal gut microbiome plays an essential role in protecting against opportunistic pathogens and maintaining immune homeostasis. Dysbiosis, an imbalance in microbial communities, is linked with disease when this imbalance disturbs microbiota functions essential for maintaining health or introduces processes that promote disease. By performing meta-analyses of many studies that have sequenced the 16S ribosomal RNA gene to characterize gut microbial communities in different disease and health contexts, we have defined very young age and Western versus Developing world/Agrarian cultures to be two major axes of gut microbiome compositional variation that are important for explaining variability across healthy humans. Interestingly, among Western adults, individuals with different diseases or microbiome disturbances have migration along both of these major axes of health-associated gut microbiome variation. For instance, obese Western individuals sometimes have microbiomes that cluster closer to Prevotella-rich/Bacteroides-poor microbiome types in the developing world and this is more common in African versus European Americans. Related to age, gut microbiomes of adults with recurrent Clostridioides difficile infection, Inflammatory Bowel Disease, cancer, and intake of broad-spectrum antibiotics all tend to cluster closer to healthy infant gut microbiomes, characterized by low diversity with increased representation of facultative versus strict anaerobes. The relationship between highly disturbed and infant gut microbiome compositions is likely related to parallel processes that occur in primary versus secondary ecological succession, where absence of a complex community of healthy gut commensals allows for the colonization of opportunistic, early succession adapted organism that undergo an ordered turnover of membership. By coupling co-occurrence patterns and longitudinal analyses of dense time-series data with genomic and metabolic network interrogations to explore underlying drivers of microbial cooperation and competition, we have been generating hypotheses regarding important interactions that occur during succession and testing them in humanized mice.

About a speaker: Dr Lozupone is a Professor in the Department of Biomedical Informatics at the University of Colorado Anschutz Medical Campus. Her research focuses on the complex community of microorganisms that inhabit the gastrointestinal tract. She has been heavily involved in the development of popular computational tools for microbial community analysis, such as the UniFrac algorithm for comparing microbial diversity among many samples using phylogenetic information. Dr. Lozupone runs an NIH funded research group that integrates integrative bioinformatics analysis of multi-omic data with experimental confirmation. Her lab is currently working to understand microbiome composition and function in a variety of disease contexts, with an emphasis on the interaction between the gut microbiome, local and systemic immune phenotypes, and metabolic co-morbidity in HIV-infected individuals and on dietary strategies to prevent Clostridioides difficile infection.